LI Xin-lan, LI Jia, WANG Yu, HUANG Man-bing, HONG Yu, CHEN Jie
Objective: To analyze and compare the cardiac toxicity risks of anthracyclines such as doxorubicin, mitoxantrone, epirubicin, daunorubicin, and idarubicin based on real-world data, and provide reference for clinical medication safety of anthracyclines. Methods: Using the search terms "doxorubicin (L01DB01)", "mitoxantrone (L01DB07)", "epirubicin (L01DB03)", "daunorubicin (L01DB02)" and "idarubicin (L01DB06)", adverse drug events (ADEs) related to cardiac toxicity were retrieved from the USA FDA Adverse Event Reporting System (FAERS) database between January 2004 and September 2023, with the above five anthracyclines as primary suspected drugs, and the epidemiological characteristics of cardiac toxicity associated with these five anthracyclines were analyzed. Results: A total of 3 159 ADE reports involving cardiac toxicity for the five anthracyclines were found in the FAERS database, including 2 215 reports for doxorubicin, 265 for mitoxantrone, 422 for epirubicin, 197 for daunorubicin, and 60 for idarubicin. For 2 215 reports of doxorubicin, 2 392 ADEs were involved with cardiac toxicity, with 62 preferred terms (PTs); the top 3 pts in terms of the quantity of ADE items were cardiac toxicity (387 cases), heart failure (354 cases), and cardiomyopathy (311 cases). For 265 reports of mitoxantrone, 663 ADEs were involved with cardiac toxicity, with 32 PTs; the top 3 pts in terms of the quantity of ADE items were tachycardia (146 cases), cardiomyopathy (103 cases), and pericardial effusion (56 cases). For 422 reports of epirubicin, 367 ADEs were involved with cardiac toxicity, with 28 PTs; the top 3 pts in terms of the quantity of ADE items were heart failure (94 cases), cardiac toxicity (36 cases), and atrial fibrillation (29 cases). For 197 reports of daunorubicin, 257 ADEs were involved with cardiac toxicity, with 25 PTs; the top 3 pts in terms of the quantity of ADE items were heart failure (31 cases), tachycardia (27 cases), and atrial fibrillation (26 cases). For 60 reports of idarubicin, 67 ADEs were involved with cardiac toxicity, with 14 PTs; the top 3 pts in terms of the quantity of ADE items were heart failure (10 cases), myocarditis (9 cases), and cardiomyopathy (7 cases). Using the reporting odds ratio (ROR) method, analysis results revealed that for doxorubicin-related ADEs, PTs with ROR above 50 included cardiac toxicity, acute cardiomyopathy, and toxic cardiomyopathy; for mitoxantrone-related ADEs, PTs with ROR above 50 included myocardial hemorrhage; for epirubicin-related ADEs, PTs with ROR above 50 included right atrial dilation and myocardial edema; no PTs with ROR above 50 were found for daunorubicin-related ADEs; for idarubicin-related ADEs, PTs with ROR above 50 included left ventricular dilation. Seven cardiac toxicity related SMQ signals were detected in the Standardised MedDRA Query (SMQ) analysis, with cardiomyopathy and heart failure as common positive signals for all five anthracyclines. Conclusion: Cardiac toxicity caused by anthracyclines is commonly associated with cardiomyopathy and heart failure. The cardiac toxicity risk intensity varies among different anthracyclines. Clinically, drugs with a lower risk of cardiac toxicity should be prioritized, and careful monitoring of cardiac toxicity related ADEs should be implemented.